title: Gastric inhibitory polypeptide receptor methylation in newly diagnosed, drug-naïve patients with type 2 diabetes: a case-control study.
abstract: GIP action in type 2 diabetic (T2D) patients is altered. We hypothesized that methylation changes could be present in GIP receptor of T2D patients. This study aimed to assess the differences in DNA methylation profile of GIPR promoter between T2D patients and age- and Body Mass Index (BMI)-matched controls. We included 93 T2D patients (cases) that were uniquely on diet (without any anti-diabetic pharmacological treatment). We matched one control (with oral glucose tolerance test negative, non diabetic), by age and BMI, for every case. Cytokines and hormones were determined by ELISA. DNA was extracted from whole blood and DNA methylation was assessed using the Sequenom EpiTYPER system. Our results showed that T2D patients were more insulin resistant and had a poorer β cell function than their controls. Fasting adiponectin was lower in T2D patients as compared to controls (7.0±3.8 µgr/mL vs. 10.0±4.2 µgr/mL). Levels of IL 12 in serum were almost double in T2D patients (52.8±58.3 pg/mL vs. 29.7±37.4 pg/mL). We found that GIPR promoter was hypomethylated in T2D patients as compared to controls. In addition, HOMA-IR and fasting glucose correlated negatively with mean methylation of GIPR promoter, especially in T2D patients. This case-control study confirms that newly diagnosed, drug-naïve T2D patients are more insulin resistant and have worse β cell function than age- and BMI-matched controls, which is partly related to changes in the insulin-sensitizing metabolites (adiponectin), in the proinflammatory profile (IL12) and we suggest in the methylation pattern of GIPR. Our study provides novel findings on GIPR promoter methylation profile which may improve our ability to understand type 2 diabetes pathogenesis.
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain ; Les Corts Primary Health Care Centre, Transverse group for research in primary care-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain ; Diabetes and Obesity Laboratory-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Canivell
authors.forename: Elena G
authors.initials: EG
authors.lastname: Ruano
authors.forename: Antoni
authors.initials: A
authors.lastname: Sisó-Almirall
authors.forename: Belchin
authors.initials: B
authors.lastname: Kostov
authors.forename: Luis
authors.initials: L
authors.lastname: González-de Paz
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Rebollo
authors.forename: Felicia
authors.initials: F
authors.lastname: Hanzu
authors.forename: Marcelina
authors.initials: M
authors.lastname: Párrizas
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
mesh_terms: D052242:Adiponectin / Q000097:blood; D000367:Age Factors; D015992:Body Mass Index; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D019175:DNA Methylation / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D018664:Interleukin-12 / Q000097:blood; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D016207:Cytokines; D011964:Receptors, Gastrointestinal Hormone; D018664:Interleukin-12; C041086:gastric inhibitory polypeptide receptor